The glomeruli are the initial site of synaptic integration in the olfactory pathway. Olfactory nerve (ON) axons from olfactory receptor neurons expressing the same odorant receptor project to the same one or few glomeruli in the main olfactory bulb, where they synapse on the apical dendrites of mitral/tufted cells (MC/TCs) and local juxtaglomerular (JG) interneurons. Each glomerulus, hence, can be considered a functional unit for processing sensory input. We hypothesize that each glomerulus is comprised of a small set of stereotyped neuron sub-types, specifically organized to perform discrete network operations. These network operations determine the transfer function from ON terminals to MCs and TCs, the output neurons of MOB. We further hypothesize that these glomerular transfer functions operate primarily on the magnitude of ON activity in each glomerulus. Analysis of patterned activity across the glomerular ensemble occurs downstream of the glomerular network. [unreadable] [unreadable] Aim 1 will identify the transmitters and receptors underlying the synaptic relationships of JG neurons. Aims 2-4 test hypotheses about three specific glomerular functions and the cellular-network mechanisms that perform these operations. Aim 2 will (i) test the hypothesis that DA- and GABAergic JG cells presynaptically inhibit ON terminals by altering Ca2+-meditaed transmitter release, and (ii) will use in vivo Ca2+ imaging and odor stimuli to test the hypothesis that presynaptic inhibition functions to scale the dynamic response range of glomerular output. Aim 3 will use in vitro and in vivo experiments to test the hypothesis that rhythmically bursting external tufted cells function to amplify and synchronize glomerular output responses to odor stimulation. Aim 4 will test the hypothesis that short axon JG cells function to mediate local, interglomerular lateral inhibition. This lateral inhibition provides interglomerular contrast enhancement that is proportional to the magnitude of ON input to each glomerulus. [unreadable] [unreadable] This renewal application builds on achievements of the previous award and uses novel approaches to clarify the organization and functions of the neural network that initiates the computation of odors.